Diagnosis and Management of DKA and Hyperglycemic, Hyperosmolar States

Transcription

1 Diagnosis and Management of DKA and Hyperglycemic, Hyperosmolar States Lindsay K. Buchert, MSN, RN, ANP-BC Department of Internal Medicine Carolinas Medical Center, Charlotte, NC 2017 Nurse Practitioner Spring Symposium Tuesday, March 28, NPSS Asheville, NC

2 Disclosures: I have no financial disclosures I will not be discussing investigational/off label uses.

3 Objectives: Describe the pathophysiology of diabetes and diabetic emergencies including DKA and hyperosmolar states. Identify pertinent signs and symptoms as well as pertinent labs needed to diagnose DKA and hyperosmolar states. Formulate a plan for the management of DKA and hyperosmolar states, including complex cases. Compare and contrast DKA and hyperosmolar states.

4 Physiology Review: Insulin: Produced by the beta cells of the pancreas, initially as the amino acid chain preproinsulin Proteolysis of preproinsulin proinsulin Proinsulin cleaved to produce C-peptide + A and B chains of insulin (21 amino acids and 30 amino acids, respectively) linked by two disulfide bonds. -Can check C-peptide to determine insulin production Insulin needed to maintain glucose homeostasis (hepatic gluconeogenesis vs. peripheral glucose uptake and use) (Powers, 2013)

5 Insulin Overview: Insulin Onset Peak (hours) Duration of Action (hours) Bolus---Rapid Acting (aspart, glulisine, lispro) Bolus---Regular (subcutaneous) Basal---NPH (isophane) Basal---Long-acting (detemir, glargine) 5-15 minutes minutes hours hours No Peak Up to 24 hours (Powers, 2013)

6 Insulin Overview: Insulin Onset Peak (hours) Duration of Action (hours) Regular U minutes 8 Up to 24 U-200 Lispro 15 minutes U-300 Glargine 6 hours No peak 36 hours Degludec (U-100 and U-200) 1 hour 9 (Tmax) ½ life of 25 hours Pre-mixed (70/30, 75/25, 50/50) 5-60 minutes Varied, multiple hours (ADA, 2015; FDA, 2015)

7 Diabetic Ketoacidosis (DKA)

8 Type 1 Diabetes 5-10% of Diabetes Auto-immune destruction of insulin-producing beta cells in the pancreas, leading to lack of insulin C-peptide low or undetectable Auto-immune markers: Islet cell autoantibodies, GAD65 autoantibodies, insulin autoantibodies, ZnT8, and tyrosine phosphatases IA-2 and IA-2β HLA alleles including DQA and DQB genes Triggers: -Possible environment factors (i.e. viruses) in those who are genetically susceptible? -Immune modulators (Cefalu, 2017; Powers, 2013)

9 Diabetic Ketoacidosis (DKA): Typically occurs in type 1 diabetes -may see ketosis-prone type 2 diabetes Need all 3 (D-K-A): 1) Diabetes/hyperglycemia 2) Ketones (serum) 3) Acidosis (metabolic, gap)

10 Differential Diagnosis: Alcoholic ketoacidosis (no hyperglycemia) Starvation ketosis (low carb diet) Anion gap acidosis: -lactic acidosis (metformin?) -aspirin or acetaminophen -methanol, ethylene glycol, propylene glycol -advanced kidney disease (Hirsch & Emmett, 2016)

11 DKA Pathophysiology: Lack of insulin (or relative lack) + increased counter-regulatory hormones (i.e. growth hormone, cortisol, etc.) + peripheral insulin resistance Inability to use carbohydrates as source of energy = increased lipolysis, free fatty acids converted to ketones Hyperglycemia, ketosis, dehydration, electrolyte imbalances (Gosmanov, Gosmanova, & Dillard-Cannon, 2014)

12 DKA Risk Factors: New diabetes diagnosis Lack of basal (long-acting) insulin Relative lack of insulin -Stress, illness, infection, steroids Insulin pump malfunction Cocaine use Psych issues/eating disorders (weight loss from skipping insulin) SGLT-2 Inhibitors (Hirsch & Emmett, 2016)

13 DKA Presentation: Rapid evolution (typically 24 hours) Initially, polyuria, polydipsia, and weight loss Later, neuro changes (lethargy, obtunded) Abdominal pain, nausea, and vomiting more common in children, but occur in adults too -delayed gastric emptying, ileus from acidosis and electrolyte abnormalities? (Hirsch & Emmett, 2016)

14 DKA Physical Exam Findings: Tachycardia Altered mental status Kussmaul s Respirations (fast, labored, and deep) Hypotension Acetone breath (fruity) (Barkley & Alvarez, 2008)

15 DKA Lab Findings: Hyperglycemia (typically mg/dl) Serum and urine ketones present -serum beta-hydroxybutyrate as measure of serum ketones (cannot be measured > 6 meq/l) Elevated anion gap -Anion gap = serum sodium (serum chloride + bicarb) Mild hyponatremia (need to correct for glucose) Elevated potassium Low CO2 Elevated BUN and creatinine Low arterial ph and P CO2 (Barkley & Alvarez, 208; Hirsch & Emmett, 2016)

16 DKA Treatment: IV insulin and IV fluids! Correct electrolyte abnormalities

17 IV Insulin in DKA: IV regular insulin bolus of 0.1 units/kg IV regular insulin infusion of 0.1 units/kg/hr Once blood glucose around 200, can decrease rate to units/kg/hr If initial potassium upon presentation is < 3.2 meq/l, wait to start insulin until potassium corrected Use of standardized infusion protocols/programs (some too aggressive?) (Gosmanov, Gosmanova, & Dillard-Cannon, 2014; Hirsch & Emmett, 2015; Powers 2013)

18 IV Fluids in DKA: IV fluid replacement to correct volume Usually start with normal saline Subsequent fluids depend on volume status, electrolytes, and urine output -Rapid correction of sodium/osmolality and blood sugar may lead to cerebral edema (pediatrics) Add dextrose to fluid once blood glucose mg/dl to prevent hypoglycemia -Allows for continuation of IV insulin as labs normalize (Gosmanov, Gosmanova, & Dillard-Cannon, 2014; Hirsch & Emmett, 2015; Powers, 2013)

19 Electrolyte Management in DKA: Maintain potassium of meq/l Bicarb use controversial (consider if ph < 6.9) as metabolic acidosis should resolve with IV insulin Phosphate usually low in DKA, but typically only needs to be replaced if < 1.0 mg/dl or if < 2.0 mg/dl with cardiac dysfunction, anemia, or respiratory depression -Risk of hypocalcemia with phosphate replacement (Gosmanov, Gosmanov, & Dillard-Cannon, 2014; Hirsch & Emmett, 2015; Powers, 2013)

20 DKA Resolution: Resolution of ketoacidosis, not hyperglycemia -Anion gap normalized ( closed ) -trending of serum beta-hydroxybutyrate Improved mental status Patient is ready to eat Treat/correct underlying cause (Gosmanov, Gosmanov, & Dillard-Cannon, 2014; Hirsch & Emmett, 2015; Powers, 2013)

21 Transition to Subcutaneous Insulin: Overlap basal insulin and IV regular insulin by 1 hour Basal bolus insulin regimen vs. insulin pump: -Need long-acting basal insulin + short-acting bolus insulin for both meals and correction Consider timing, use of NPH as a bridge to long-acting insulin Consider IV insulin rate vs. home dose vs. weight-based regimen Typically 0.5 units/kg insulin requirement in type 1 diabetes -May need more if under stress Continue to treat underlying cause Outpatient follow-up at discharge (Gosmanov, Gosmanov, & Dillard-Cannon, 2014; Hirsch & Emmett, 2015; Powers, 2013)

22 Basal-Bolus Insulin Regimen Breakfast Lunch Dinner Basal

23 Blood Sugar (mg/dl) Basal Plus Sliding Scale Alone units 6 units 6 units units 0 units Time (24 hours)

24 Special Considerations in DKA: Insulin pumps Treatment of DKA on the floor Pregnancy Euglycemic DKA (SGLT-2 Inhibitors) Recurrent DKA

25 DKA and Insulin Pumps: DKA due to insulin pump malfunction: -Tubing kinked/dislodged -Bad insulin -Lack of supplies -Pump itself not working properly Remove insulin pump once placed on IV regular insulin Troubleshoot pump Overlap insulin pump and IV regular insulin by 1 hour when resuming insulin pump

26 Management of DKA on the Floor: Can be considered with mild, uncomplicated DKA Requires subcutaneous rapid acting insulin administered every 1-2 hours until DKA resolution -Caveat: Insulin will stack Can be cost-effective (same time until DKA resolution, same amount of insulin, and same length of stay, without the ICU), but must have adequate training, staffing, and resources (Gosmanov, Gosmanov, & Dillard-Cannon, 2014; Hirsch & Emmett, 2015)

27 DKA in Pregnancy: Occurs in 0.5-3% of diabetic pregnancies Pregnancy = insulin resistance -Plus potential need for steroids? Similar presentation to DKA outside pregnancy DKA can occur with a much lower blood glucose level (< 200 mg/dl) in pregnancy due to increased fetal glucose needs OB emergency due to fetal mortality risk (9-36%) and risk for pre-term labor Treatment the same as outside pregnancy, but with fetal heart monitoring Need for transition of care in teen pregnancy (Ecker, 2017)

28 Euglycemic DKA: Seen with SGLT-2 inhibitors (-liflozin), pregnancy, starvation, or recent insulin administration prior to arrival in the hospital Both type 1 and type 2 diabetes Usually seen after stress (MI/CVA), surgery, excessive exercise, or fasting Normoglycemic but the rest of the labs point to DKA Given normal blood sugar (or lower than typically seen in DKA), may be easy to miss -consider in cases of anion-gap acidosis that don t resolve Mechanism of action: Increased loss of glucose through the kidney, lower insulin dose from SGLT-2 addition (and increased plasma glucagon levels, leading to increased ketone production), but more insulin resistant due to stress, illness, etc. Prevention?: Stop SGLT-2 inhibitors before scheduled surgery, fasting, or excessive exercise (i.e. a marathon), avoid overly low carb diets, and avoid excessively decreasing insulin doses Treatment: Stop SGLT-2 Inhibitor and treat DKA (Handelsman, et al., 2016; Hirsch & Emmett, 2016; Peters et al., 2015)

29 Recurrent DKA: Proposed risk factors: -younger age at diagnosis, gender (male > female), females < age 35, high A1C, comorbidities (especially depression, substance abuse), socioeconomic status ABCDs: Statistically significant risk factors found in 2017 study: 1) Age < 35 2) Behavioral Health: History of depression 3) Coverage: Self-pay/lack of private insurance 4) Drug/alcohol abuse *A1C >10.6% was not significantly significant, but study underpowered (Bradford, Crider, Xu, & Naqvi, 2017)

30 Preventing Recurrent DKA: Pediatric study (majority of participants with DKA 3-9x/year): Behavioral Therapy: -Problem solving, communication skills, cognitive restructuring, family systems changes Care Coordination: -Transportation, supplies, follow-up, regularly interacting with diabetes care team Case Management: -Assistance with drug/alcohol treatment *Also consider simplifying insulin regimen as much as possible (Pump candidate?) (Harris, et al., 2014)

31 Hyperglycemic, Hyperosmolar, Non-Ketotic States (HHNK) or Hyperglycemic, Hyperosmolar States (HHS)

32 Type 2 Diabetes: Insulin resistance and impaired insulin secretion Often associated with abnormal fat metabolism and increased hepatic glucose production Early increased insulin production to compensate for resistance This is unsustainable long-term, leading to eventual decreased insulin secretion and finally, failure of beta cells to produce insulin (Powers, 2013)

33 Hyperglycemic, Hyperosmolar State (HHS): Typically occurs in type 2 diabetes -Reminder: May see ketosis prone type 2 diabetes

34 HHS Pathophysiology: Caused by relative lack of insulin and inadequate fluid intake, leading to hyperglycemia Hyperglycemia causes osmotic diuresis, leading to volume depletion, worsened by poor fluid replacement Unclear why the lack of ketones: -Relative vs. absolute insulin deficiency? -Lower counter-regulatory hormones and free fatty acid levels? -Liver less capable of ketone synthesis vs. insulin/ ketogenesis (Powers, 2013) glucagon ratio less favorable for

35 HHS Risk Factors: New diagnosis of diabetes Dehydration TPN/high calorie/high carb continuous nutrition Medications (thiazide diuretics, steroids) Pancreatitis Stress/illness Advanced age (Barkley & Alvarez, 2008)

36 HHS Presentation: Generally evolves over a prolonged period of time Polyuria, polydipsia, and weight loss from prolonged hyperglycemia Weakness Neuro changes, including obtundation and common (Hirsch & Emmett, 2016)

37 HHS Physical Exam Findings: Altered mental status Dehydration: -poor skin turgor, dry oral mucosa Tachycardia Hypotension Shallow breathing (Barkley & Alvarez, 2008; Hirsch & Emmett, 2016)

38 HHS Lab Findings: Hyperglycemia: Often > 1,000 mg/dl Elevated effective plasma osmolality: > 320 mosmol/kg -Effective plasma osmolality = portion of osmolality from sodium and glucose Mild hyponatremia Elevated BUN and creatinine Normal anion gap, lack of serum ketones

39 HHS Treatment: IV fluids and IV insulin! See DKA treatment regarding IV fluids and IV insulin on previous slides IV fluids often go a long way in improving glycemic control and electrolyte imbalances, but still need IV insulin Risk of worsening neuro status if fluids replaced too rapidly due to prolonged onset of symptoms (Powers, 2013)

40 HHS Resolution: Resolution = Improved mental status + plasma effective osmolality < 315 mosmol/kg Alert and ready to eat Transition to subcutaneous basal insulin (1-hour overlap with IV insulin) Use of basal-bolus insulin (basal insulin + mealdependent rapid-acting insulin + correction dose rapidacting insulin) Will likely need to be discharged home on insulin, but may be able to transition to oral medications outpatient Early outpatient follow-up (Hirsch & Emmett, 2015; Powers, 2013)

41 Conclusion---DKA vs. HHS: DKA HHS Diabetes Type Usually Type 1 Type 2 Onset Rapid (24 hours) Gradual Blood Glucose mg/dl > 1,000 mg/dl Serum Ketones Present Usually Absent, low Anion Gap Elevated Usually normal Serum Osmolality mosmol/kg mosmol/kg Other Findings Acetone breath, Kussmaul s Altered mental status Diagnostic Criteria BG, anion gap metabolic acidosis, serum ketones BG, elevated osmolality, neuro changes Treatment IV Insulin and IV fluids IV Fluids and IV insulin Resolution Anion gap normalized, ketones improved Alert, osmolality < 315 mosmol/kg Discharge Plan Subcutaneous insulin Subcutaneous insulin

42 References: American Diabetes Association. (2015, March/April). Insulins Available in the United States. Retrieved from Diabetes Forecast website: Barkley, T.W. Jr. & Alvarez, H. (2008). Diabetic Emergencies. In T. W. Barkley Jr. and C. M. Myers (Eds.), Practice Guidelines for Acute Care Nurse Practitioners (2 nd ed.), (pp ). St. Louis, MO: Saunders Elsevier. Bradford, A.L., Crider, C. C.., Xu, X., & Naqvi, S. H. (2017), Predictors of recurrent hospital admission for patients presenting with diabetic ketoacidosis and hyperglycemic hyperosmolar state. Journal of Clinical Medical Research, 9(1), DOI: Cefalu, W.T. (Ed.). (2017). American Diabetes Association Standards of Medical Care in Diabetes 2017 [Special Section]. Diabetes Care, 40(Supplement 1). Ecker, J. L.. (2017, January). Pregestational diabetes mellitus: Obstetrical issues and management.. In M. F. Greene & V. A. Barss (Eds.), UpToDate. Retrieved January 16, 2017 from Gosmanov, A. R., Gosmanova, E. O., & Dillard-Cannon, E. (2014). Management of adult diabetic ketoacidosis. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 7, Handelsman, Y., Henry, R. R., Bloomgarden, Z. T., Dagogo-Jack., S., DeFronzo, R. A., Einhorn, D., Weir, M. R. (2016). American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of SGLT-2 inhibitors and diabetic ketoacidosis, 22(6). Retrieved from Harris, M. A., Wagner, D. V., Heywood, M., Hoehn, D., Bahia, H., & Spiro, K. (2014, June). Youth repeatedly hospitalized for DKA: Proof of concept for novel interventions in children s healthcare (NICH). Diabetes Care, 37, e125-e126. DOI: /cd Hirsch, I. B., & Emmett, M. (2015, December). Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment. In D. M. Nathan & J. E. Mulder (Eds.), UpToDate. Retrieved November 30, 2016 from Hirsch, I. B., & Emmett, M. (2016, December). Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Clinical features, evaluation, and diagnosis. In D. M. Nathan & J. E. Mulder (Eds.), UpToDate. Retrieved January 16, 2017 from Peters, A. L., Buschur, E. O., Buse, J. B., Cohan, P., Diner, J. C., & Hirsch, I.B. (2015, September). Euglycemic diabetic ketoacidosis: A potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care, 38, Powers, A.C. (2013). Diabetes Mellitus. In J.L. Jameson (Ed.), Harrison s Endocrinology (pp ). New York, NY: McGraw Hill Education. U.S. Food and Drug Administration (2015, September). Tresiba (insulin degludec injection) label (Reference ID: ). Retrieved from

43 Acknowledgements: Thank you to Dr. Kelli Dunn for reviewing this presentation.

44 Questions?

45 Thank You 2017 NPSS ASHEVILLE, NC